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Nesina

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Nesina

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Pancreatitis

There have been postmarketing reports of acute pancreatitis in patients taking NESINA. After initiation of NESINA, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, NESINA should promptly be discontinued and appropriate management should be initiated. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using NESINA.

Hypersensitivity Reactions

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with NESINA. These reactions include anaphylaxis, angioedema, and severe cutaneous adverse reactions including Stevens-Johnson syndrome. If a serious hypersensitivity reaction is suspected, discontinue NESINA, assess for other potential causes for the event, and institute alternative treatment for diabetes [see ADVERSE REACTIONS]. Use caution in a patient with a history of angioedema with another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with NESINA.

Hepatic Effects

There have been postmarketing reports of fatal and non-fatal hepatic failure in patients taking NESINA, although some of the reports contain insufficient information necessary to establish the probable cause [see ADVERSE REACTIONS]. In randomized controlled studies, serum alanine aminotransferase (ALT) elevations greater than three times the upper limit of normal (ULN) were observed: 1.3% in alogliptin-treated patients and 1.5% in all comparator-treated patients.

Patients with type 2 diabetes may have fatty liver disease which may cause liver test abnormalities, and they may also have other forms of liver disease, many of which can be treated or managed. Therefore, obtaining a liver test panel and assessing the patient before initiating NESINA therapy is recommended. In patients with abnormal liver tests, NESINA should be initiated with caution.

Measure liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. In this clinical context, if the patient is found to have clinically significant liver enzyme elevations and if abnormal liver tests persist or worsen, NESiNa should be interrupted and investigation done to establish the probable cause. NESINA should not be restarted in these patients without another explanation for the liver test abnormalities.

Use with Medications Known to Cause Hypoglycemia

Insulin and insulin secretagogues, such as sulfonylureas, are known to cause hypoglycemia. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with NESINA.

Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with NESINA or any other antidiabetic drug.

Patient Counseling Information

See FDA-Approved Patient Labeling (Medication Guide)

Instructions

Inform patients of the potential risks and benefits of NESINA.

Patients should be informed that acute pancreatitis has been reported during use of NESINA. Patients should be informed that persistent, severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Patients should be instructed to promptly discontinue NESINA and contact their physician if persistent severe abdominal pain occurs.

Patients should be informed that allergic reactions have been reported during use of NESINA. If symptoms of allergic reactions (including skin rash, hives, and swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, patients should be instructed to discontinue NESINA and seek medical advice promptly.

Patients should be informed that postmarketing reports of liver injury, sometimes fatal, have been reported during use of NESINA. If signs or symptoms of liver injury occur, patients should be instructed to discontinue NESINA and seek medical advice promptly.

Inform patients that hypoglycemia can occur, particularly when an insulin secretagogue or insulin is used in combination with NESINA. Explain the risks, symptoms, and appropriate management of hypoglycemia.

Instruct patients to take NESINA only as prescribed. If a dose is missed, advise patients not to double their next dose.

Instruct patients to read the Medication Guide before starting NESINA therapy and to reread each time the prescription is refilled. Instruct patients to inform their healthcare provider if an unusual symptom develops or if a symptom persists or worsens.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Rats were administered oral doses of 75, 400, and 800 mg/kg alogliptin for 2 years. No drug-related tumors were observed up to 75 mg/kg or approximately 32 times the maximum recommended clinical dose of 25 mg, based on AUC exposure. At higher doses (approximately 308 times the maximum recommended clinical dose of 25 mg), a combination of thyroid C-cell adenomas and carcinomas increased in male but not female rats. No drug-related tumors were observed in mice after administration of 50, 150, or 300 mg/kg alogliptin for 2 years, or up to approximately 51-times the maximum recommended clinical dose of 25 mg, based on aUc exposure.

Alogliptin was not mutagenic or clastogenic, with and without metabolic activation, in the Ames test with S. typhimurium and E. coli or the cytogenetic assay in mouse lymphoma cells. Alogliptin was negative in the in vivo mouse micronucleus study.

In a fertility study in rats, alogliptin had no adverse effects on early embryonic development, mating, or fertility, at doses up to 500 mg/kg, or approximately 172-times the clinical dose based on plasma drug exposure (AUC).

Use In Specific Populations

Pregnancy

Pregnancy Category B

No adequate or well-controlled studies in pregnant women have been conducted with NESINA. Based on animal data, NESINA is not predicted to increase the risk of developmental abnormalities. Because animal reproduction studies are not always predictive of human risk and exposure, NESINA, like other antidiabetic medications, should be used during pregnancy only if clearly needed.

Alogliptin administered to pregnant rabbits and rats during the period of organogenesis was not teratogenic at doses of up to 200 and 500 mg/kg, or 149-times and 180-times, respectively, the clinical dose based on plasma drug exposure (AUC).

Doses of alogliptin up to 250 mg/kg (approximately 95-times clinical exposure based on AUC) given to pregnant rats from gestation day 6 to lactation day 20 did not harm the developing embryo or adversely affect growth and development of offspring.

Placental transfer of alogliptin into the fetus was observed following oral dosing to pregnant rats.

Nursing Mothers

Alogliptin is secreted in the milk of lactating rats in a 2:1 ratio to plasma. It is not known whether alogliptin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when NESINA is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of NESINA in pediatric patients have not been established.

Geriatric Use

Of the total number of patients (N=8507) in clinical safety and efficacy studies treated with NESINA, 2064 (24.3%) patients were 65 years and older and 341 (4%) patients were 75 years and older. No overall differences in safety or effectiveness were observed between patients 65 years and over and younger patients. While this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.

Hepatic Impairment

No dose adjustments are required in patients with mild to moderate hepatic impairment (Child-Pugh Grade A and B) based on insignificant change in systemic exposures (e.g., AUC) compared to subjects with normal hepatic function in a pharmacokinetic study. NESINA has not been studied in patients with severe hepatic impairment (Child-Pugh Grade C). Use caution when administering NESINA to patients with liver disease [see WARNINGS AND PRECAUTIONS].

Last reviewed on RxList: 2/11/2013
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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